My truck has a 283 bored to 0.060"-over, an RV cam, and (currently) an Edelbrock Performer manifold with a Holley Economaster 4-bbl on it. It delivers 450 cfm, and has decent response and good gas mileage (I get 14-16 in town consistently, and up to 19 on the highway, depending on how fast I drive - usually 60-65 - and wind). I also have an SM420 transmission with a 3.08 rear end.

Here's my question:

Given my setup, which one would you say I should use? I want better response (when needed), but decent economy.

Getting 15 mpg in everyday driving in one of these trucks is impressive, let alone 19 mpg peak. I don't think there's any way to improve on that in one of these trucks. Heck, the new trucks with the 5.3L won't do significantly better. While you should be able to add some performance to that engine with EFI, I'm not sure it will be that noticeable. The main reason for going EFI, in my opinion, is drivability. As far as which one to choose, the 2bbl version will definately be the one to choose. At 800cfm, the 4bbl version is too much for the 283.
Personally, I've been sold on EFI since the 90's and installed a Holley Pro-Jection system ('97?) in my truck; then a TPI system from an '86 Vette ('00?). The best thing about EFI for my truck was the fact that it ran like a new truck. Turn the key, and it starts and runs without the engine being "cold blooded". The Pro-jection did that fine, but there wasn't enough range in the adjusting screws and the truck always ran rich. I don't have experience with the newer systems but one would assume that Holley has improved their system in the last 20 years.
After being disappointed in the efficiency of the Pro-jection on a 327, I turned to the GM TPI system and learned how to program it. With that setup, I would get 16 mpg on the highway with my 327 / 300hp cam and 5 speed and 3:73 gears. It was an improvement over my Holley carb in both performance and efficiency, but not earth shattering. I don't think you'll get more efficiency than you're already getting regardless of what you do.
If you want to maintain efficiency and gain some performance, I'd probably be looking more at your transmission and rear end ratio. I see you have a 3.08 gear ratio, which I assume you put in to maximize fuel economy. If you had left the 3.73 gear ratio in place and added a 5 speed, you would gain a lot of acceleration and still had a lower final gear ratio with a ~0.7 overdrive.
There are several threads on this forum that discuss swapping in a 5 speed, so I won't discuss it here unless needed.

I talked extensively this morning with an older tech guy at Holley. He was very helpful. He told me that the Snyper EFI would probably maintain my current MPG, and that it might improve it, but probably only slightly. He also said that, in all reality, that a properly tuned carburetor will get just as good gas mileage as the EFI. He also said the 2-bbl unit was for Fords, not Chevys, so that's a no-go.

Since I am looking for economy with improved power (the current Holley is 450 cfm), he really encouraged me to go with a Holley 1850SA, which is a 600cfm, 4-bbl carburetor with the larger rear ports, which would give me the best of both worlds.

My son thinks I should go with the Snyper EFI, because he says it gives me the ability to automatically adjust the timing, which my distributor is setup for, and it can also automatically adjust the fuel mixture and flow, as needed by the engine.

It's a LOT of money ($1250) to drop into it, especially if my ROI is going to be minimal, although my son thinks the ability to fine tune it for my vehicle, coupled with the self-learning and self-adjusting ability makes it worth it.

I think the advice you're getting from both the Holley tech and your son is sound. It's just a matter of priorities and what it's worth to you. The ability of the computer to adjust everything on the engine allows it to be maximized in all aspects. However, don't expect big gains in performance and your efficiency is already good.
As I said, I'm a big fan of EFI systems, but they're not free. The Holley system is going to be easy to install and should give you years of trouble-free driving. The hardest part of the Pro-Jection install was the fuel lines, and that wasn't that hard. The first time I put in the return line, I just used a fitting and ran the line into the metal fuel filler tube. That worked, but I didn't like it, so I ended up drilling a hole in the fuel level sensor flange and welding a return port to the top.
The reason I went to the GM systems is that they are much cheaper to install and have all the self-tuning ability you want. However, you have to do a lot of research into the wiring and programming aspects. The information is all online, but it adds a lot of work, and there's no tech help line if things aren't working.
For my truck, the TPI engine was sold awhile ago and I'm planning on a LSx engine transplant in the future. I only spent $1000 on a '04 5.3L with 75,000 miles with computer and accessories, and another $400 on the 4L65E transmission for it. After selling off the Corvette TPI system for $650 and the tired 327 for $300, I'll only have $500 into the upgrade, and that's before I sell of the NV3500 I had in the truck.

While I understand the advantages to the EFI system, I wonder if it will give me a reasonable ROI.

Other than price, my biggest hesitation about the EFI system is long-term serviceability. I have been involved in professional audio/electronics for most of my life, and I am well aware of how fast electronic devices can become obsolete and parts, if available at all, can get outrageously expensive. Of course, anything computer related, like the on board computer control system used in the Holley, is obsolete the day it is released, and I am quite concerned that, at some point, upgrades will no longer be available for it (if they ever do have them in the first place), and I'll be up a creek without a paddle. I really DON'T want to do this twice...

I'm leaning towards the Holley 0-1850SA, which the Holley tech recommended. If I order it from Summit, which has a good price and free shipping, I can return it for a full refund if I don't like it.

Your concerns are definitely valid. That was another reason I went with GM parts. I wasn't sure how long Holley would support their 1st generation fuel injection system, and I figured somebody would maintain the GM stuff in one way or another for a long time. Of course, with Holley I'd expect them to back up their products too. I just went online and they still have the ECU for the Pro-Jection listed, but you can't order it online. Don't know whether that means that it's not available, but that is a 20 year old system. There are other options these days too. There's a product called MegaSquirt that is designed to run any fuel injected engine. it's universal and requires you to use their software to tune the engine, but it would be a backup plan.
I will say that my experience with carburetors and fuel injection would suggest that you're going to end up needing a rebuilt carburetor in 10 years, but the injection systems last 20 before they need to be rebuilt.
As far as the NV3500 I have, I hadn't really thought about selling it, but since I have the 4L65E now, I would consider it. The biggest hurdles to installing it are the electronic speedo and the hydraulic clutch. There's a person online who will sell a kit to mount a hydraulic clutch master in our trucks, and I could get you that link. When I installed mine, the kit wasn't available, so I mounted a dual master cylinder from a '62 truck and had a custom line made. The electronic speedo can be solved using a 3rd party conversion box that will run a motor to your speedo, but it's $300 from Dakota Digital. You also need a crossmember from an Automatic truck to hold up the back of the transmission. Lastly, the crossmember that holds up the motor mounts to the bellhousing needs to be notched or removed.
If you're still interested in that conversion, I live in Richland, WA. I bought the transmission online and shipping wasn't actually that bad. I would sell you all the parts I don't need if you want to go that route. Of course, to really get a performance boost, you'd have to change out the rear gears also.

I ended up looking around online and found a NOS Holley 1850C on Facebook Marketplace for $150. The guy bought it, installed it on the engine in his truck he was working on, then decided to change the heads, which necessitated changing the carburetor. So, he took it off, put it in the house on a shelf, and let it sit there for 6 or so months. Seeing as how it was 1/2 the price of a new one, AND it was setup for a manual choke, I went and got it (he was only about 45 miles from me).

I installed it, but found I had a heat issue that caused perculation, so I installed a 1" phenolic spacer, replaced the top plate to carb bottom gasket, which had cooked pretty good and was leaking, then reinstalled the 1850. After setting the primaries, idle speed, and throttle speed when using the choke, I started driving and tweaking it. So far, all seems OK.

I'm not sure what the mileage will come out to once I get it dialed in, but I have an in-dash vacuum gauge and I can see that it's not wasting too much fuel for normal driving conditions. It has a lot more power, which I expected, too.

I have to drive it from Tulsa to Kansas City next week, which will give me a good opportunity to see how it does with the 1850 as opposed to the 4360 Economaster.

Thanks for the update. It's always good to close the loop on these threads. So often I'm reading a thread with people asking the same question as I have, only to not have the question answered. You always wonder if they gave up or solved the problem and didn't report back.